2-Alkyl-4-halo-5-formylimidazoles find application as starting materials for the production of drugs, such as diuretics, antihypertensive drugs, etc. and, as such, are attracting much attention but there is little literature on the methodology for their production. Thus, all that is known is the method starting with 2-amino-3,3-dichloroacrylonitrile and an aldehyde and involving the formation of a Schiff base (cf. Japanese Patent Application Kokai No. 148788/1979).
However, this method was found to be not satisfactory in that the starting compound 2-amino-3,3-dichloroacrylonitrile was not easily available, thus being a serious deterrent to commercial scale production. Therefore, the development of a new production process for 2-alkyl-4-halo-5-formylimidazoles was awaited in earnest by the industry.
Under the circumstances the inventors of this invention discovered a new production process comprising halogenating 2-alkyl-5-formylimidazoles with an N-halosuccinimide to give 2-alkyl-4-halo-5-formylimidazoles and filed a Japanese patent application No. 18717/1991 (Japanese Patent Application Kokai No. 327575/1992) and the corresponding U.S. patent application (U.S. application Ser. No. 07/999,134 (CIP Application). Incidentally, regarding the process for producing 2-alkyl-5-formylimidazoles, the inventors filed Japanese Patent Applications No. 51515/1993 and No. 51516/1993 and the corresponding U.S. patent application (U.S. application Ser. No. 08/125,220).
However, this process comprising halogenating an 2-alkyl-5-formylimidazole with an N-halosuccinimide entails the by-production of the 2-alkyl-4,5-dihaloimidazole to detract from the yield of the object compound. This necessitates a purification step but the inventors' investigation revealed that the above byproduct could not be sufficiently removed by the usual purification procedures such as recrystallization from a solvent, pH fractional crystallization, active carbon treatment, etc.
The object of this invention is, therefore, to provide a commercially useful purification method for 2-alkyl-4-halo-5-formylimidazoles, by which the impurity 2-alkyl-4,5-dihaloimidazoles can be efficiently removed.